The principal objectives of this proposal are: a) To investigate the metabolic regulation of skeletal muscle blood flow, b) To determine the time course of the release of vasoactive agents in relation to the changes in vascular resistance and oxygen consumption and c) To determine the effects of an alteration in substrate availability and utilization on the control of blood flow. Since substrate utilization and oxidative capacity correlate with muscle fiber type, the study of muscle of relatively homogenous fiber types provides a unique opportunity for testing the current concepts regarding the metabolically-linked local regulation of blood flow. The soleus muscle of the cat will be utilized as the high oxidative muscle and the flexor digitorum longus and flexor hallicus longus muscles as the low oxidative muscles. The time course of the changes in venous plasma K ion, osmolality and inorganic phosphate and tissue adenosine in relation to the changes in vascular resistance and oxygen consumption will be followed at various levels of tension development. To be able to understand the relationship between metabolism and blood flow, it is necessary to have a better understanding of skeletal muscle metabolism. Therefore, the relative contribution of plasma glucose and free fatty acids and endogenous substrates (glycogen and triglycerides) to the oxygen consumption of the muscle at different work loads will be determined. The link between metabolism and blood flow will be further defined by studying the regulation of blood flow in cats made diabetic with alloxan and in cats treated with thyroxin. These experiments should provide a clearer understanding of the possible mediators of active hyperemia and the effect of skeletal muscle metabolism on the regulation of its blood flow.